ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Addictive Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1627477
This article is part of the Research TopicWomen in Psychiatry 2024: PsychopharmacologyView all 6 articles
AMPA/kainate receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving
Provisionally accepted
Laura Huerta Sanchez
Mirette G TadrosHoa H T DoanSylvie V Vo
Sanil R ChaudhariTaylor L LiPeter B JamesAudrey Y NaFernando J CanoTod E Kippin
Karen K Szumlinski*- Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, United States
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The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. To investigate the role of mPFC AMPA receptors (AMPARs) in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPA/kainate receptor antagonist NBQX (0 or 1 µg/0.5 µl per side), followed by 30-min tests for cue-induced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine-and sucrose-craving to AMPAR subunit expression within mPFC subregions. Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. In contrast, an intra-PL NBQX infusion increased cue-induced cocaineseeking in female rats tested in early withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Together, these findings indicate a necessary role for AMPAR/kainate receptors within the PL in driving incubated cocaine-craving and suggest that AMPAR/kainate receptors located within the IL may be involved also in sucrose-craving selectively in males.
Keywords: Incubation of drug craving, incubation of sucrose craving, Prefrontal Cortex, AMPA receptors, drug craving
Received: 12 May 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Huerta Sanchez, Tadros, Doan, Vo, Chaudhari, Li, James, Na, Cano, Kippin and Szumlinski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Karen K Szumlinski, Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, United States
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